Resistance After Single-Dose Nevirapine Is Time Related


SAN FRANCISCO — Pregnant women given a single dose of nevirapine during pregnancy to prevent vertical transmission of HIV were more likely to fail their own HIV treatment if it was started within 6 months of taking the nevirapine, Shahin Lockman, M.D., reported.

The randomized study of 218 women and 30 infants in Botswana found that, for the cohorts as a whole, the peripartum nevirapine dose led to higher rates of virologic failure in women and their infants, compared with women who received a peripartum dose of placebo and their infants, she said at the annual meeting of the Infectious Diseases Society of America.

Most resource-poor nations include nevirapine in their first-line treatment regimens for women and infants. More than 500,000 women each year are believed to receive single-dose nevirapine during pregnancy. This is a simple and affordable measure that halves the risk of vertical transmission, but previous data suggest that it can cause resistance to subsequent nevirapine therapy in 25%–70% of women and 40%–90% of infants, said Dr. Lockman of Brigham and Women's Hospital, Boston.

The current data came from the Mashi study of 12,000 HIV-infected women and 491 infants randomized to receive a single peripartum dose of nevirapine or placebo plus a short course of zidovudine starting at 34 weeks' gestation. Infants received 1 month of zidovudine if formula-fed or 6 months of zidovudine if breast-fed.

Women who developed an AIDS-defining illness or whose CD4 counts fell below 200 cells/mm

Of the 218 women who started antiretroviral therapy and had adequate follow-up, 18% of 112 who previously received single-dose nevirapine and 5% of 106 who previously received single-dose placebo developed virologic failure by 6 months after starting the combination antiretroviral regimen.

At 12 months, 20% of the nevirapine group and 10% of the placebo group had developed virologic failure, defined as an HIV RNA load greater than 400 copies/mL. At 24 months, 28% of the nevirapine group and 11% of the placebo group had failed combination therapy. All differences were statistically significant.

Further analysis showed that the failures occurred in women who started their antiretroviral therapy within 6 months of receiving the single dose of nevirapine but not in women whose therapy began at least 6 months after the single nevirapine dose.

Of the 60 women who started combination antiretroviral therapy within 6 months of the peripartum dose, 42% of the 24 women in the nevirapine group and none of the 36 women in the placebo group developed virologic failure by 6 months. Virologic failure was seen at 12 and 24 months in 46% of the nevirapine group and 3% of the placebo group. All differences were highly significant.

Virologic failure rates did not differ significantly between the nevirapine and placebo groups in the 158 women who started combination therapy at least 6 months after the peripartum dose.

A total of 30 HIV-infected infants were given the same combination antiretroviral therapy. Of 15 infants whose mothers got single-dose nevirapine during pregnancy, 10 developed virologic failure during 2 years of follow-up, compared with 2 of 15 infants in the placebo group. Two infants in the nevirapine group and three in the placebo group died.

Infants in the nevirapine group showed a smaller increase in CD4 counts on combination therapy vs. those in the placebo group. For mothers, the CD4 counts did not differ significantly between groups.

Only nevirapine exposure predicted the risk of virologic failure in women and infants. Other factors such as maternal age, clinic location, or infant feeding strategy (breast vs. formula) were not predictors.

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